Role of prostaglandin E2 in mediating the effects of pH on the hydroosmotic response to vasopressin in the toad urinary bladder.
Acidosis inhibits the hydroosmotic response to vasopressin. Since prostaglandins are known to modulate vasopressin-stimulated water flow we investigated the role of endogenous prostaglandin E2(PGE2) production in the pH-dependent response of the toad urinary bladder to vasopressin. Graded acidification of the serosal medial resulted in a progressive decline in vasopressin-stimulated water flow from 26.6 +/- 0.5 mg/min at pH 8.4 to 1.7 +/- 0.6 at pH 6.9. In these bladders basal PGE2 synthesis increased from 5.09 +/- 0.51 pmol/min per g hemibladder at pH 8.4 to 18.8 +/- 2.8 at pH 6.9. The addition of that concentration of PGE2 produced by the bladder at pH 7.4 (4 nM) to bladders at pH 8.4 resulted in 62-71% of the inhibition usually seen at pH 7.4; these data suggest that basal PGE2 production per se and not other products of prostaglandin synthesis or other pH-dependent events is responsible for the effect of acidosis. Preincubation with prostaglandin synthesis inhibitors reversed in major part the effect of serosal acidification on the response to submaximal concentrations of vasopressin and completely abolished the effect of pH on near maximal concentrations of the hormone. An increase in PGE2 synthesis after vasopressin was not seen at any pH. These studies establish that increased basal PGE2 synthesis plays a critical role in the pH dependence of the hydroosmotic response to vasopressin and demonstrate that factors that modulate the response to vasopressin may exert this effect by changing the basal rate of prostaglandin synthesis.
D000138:Acidosis / Q000503:physiopathology; D000818:Animals; D002024:Bufo marinus; D015232:Dinoprostone; D005260:Female; D006863:Hydrogen-Ion Concentration; D009995:Osmosis / Q000187:drug effects; D011458:Prostaglandins E / Q000096:biosynthesis / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology*
D011458:Prostaglandins E; D014667:Vasopressins; D015232:Dinoprostone